Fold-recognition analysis predicts that the Tag protein family shares a common domain with the helix-hairpin-helix DNA glycosylases

The Escherichia coli protein Tag is traditionally regarded as an archetype of one of four classes of N-alkylpurine DNA glycosylases. However, its structure and phylogenetic relationship to other glycosylases remains a mystery. Fold-recognition and sequence profile analyses suggest that Tag shares the catalytic domain with helix-hairpin-helix (HhH) glycosylases such as MutY, AlkA and EndoIII, but its N- and C-termini together form a unique His(2)Cys(2) cluster. The findings presented in this paper provide insight into sequence-structure-function relationships in the Tag family and should aid in a more precise definition of the common core of the HhH superfamily of glycosylases involved in DNA repair. (C) 2002 Elsevier Science B.V. All tights reserved.